I plan to continue my studies defining the protein composition of two brain membranes of different cellular origin (myelin synthesized by oligodendroglial cells and nerve ending membrane synthesized by neuronal cells), and then to study the metabolism and to trace the path by which individual proteins are integrated into the developing membrane. The effects of metabolic insults on the assembly of these membranes and metabolism of individual proteins will be studied at different stages in development of the rat. Much of the background information concerning myelin metabolism is already available and studies of myelinogenesis in young rats made hypothyroid by methimazole treatment and hyperthyroid by injection with thyroxin will be initiated. Incorporation of radioactive amino acids into individual proteins of myelin of animals in different thyroid states will be compared. Studies of nerve ending membrane (synaptic plasma membrane and vesicle membrane) will initially concentrate on developing methods for the study of protein composition and metabolism of nerve endings specific to certain pharmacologically defined pathways. One experimental approach is to treat animals pharmacologically to destroy certain pathways (e.g., 6-hydroxydopamine to destroy catecholaminergic pathways) and, by comparison with control animals, decide which proteins of the nerve ending membrane fraction are specific to the lesioned pathway. The specificity of this approach will be increased by using double label isotope techniques, and by comparing proteins that are labelled only by axonal transport to proteins labeled by local incorporation. Identification of specific nerve ending proteins will allow us to investigate their metabolism as a function of metabolic during development.